Properties of low-threshold motor axons in the human median nerve

This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na(+) conductance, I(NaP). Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I(NaP). Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I(h)) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.

Low-threshold monopolar motor mapping for resection of primary motor cortex tumors

Microsurgery within eloquent cortex is a controversial approach because of the high risk of permanent neurological deficit. Few data exist showing the relationship between the mapping stimulation intensity required for eliciting a muscle motor evoked potential and the distance to the motor neurons; furthermore, the motor threshold at which no deficit occurs remains to be defined.

Low-threshold monopolar motor mapping for resection of lesions in motor eloquent areas in children and adolescents

Object Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents. Methods The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation. Results The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm(3)) in 1 patient. Conclusions High-frequency train-of-five with a minimal threshold of 1-3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis

BACKGROUND: Number of intratumoral mast cells predicts survival in various cancers. The prognostic significance of such mast cells in surgically treated prostate cancer is unknown. METHODS: Mast cell densities were determined in prostate cancer samples of more than 2,300 hormone-naïve patients using a tissue microarray format in correlation with clinical follow-up data. Mast cells were visualized immunohistochemically (c-kit). All patients were homogeneously treated by radical prostatectomy at a single institution. RESULTS: Mast cells were present in 95.9% of the tumor samples. Median mast cell number on the tissue spot was 9 (range: 0-90; median density: 31 mast cells/mm(2)). High mast cell densities were significantly associated with more favorable tumors having lower preoperative prostate-specific antigen (P = 0.0021), Gleason score (P < 0.0001) and tumor stage (P < 0.0001) than tumors with low mast cell densities. Prostate-specific antigen recurrence-free survival significantly (P = 0.0001) decreased with decline of mast cell density showing poorest outcome for patients without intratumoral mast cells. In multivariate analysis mast cell density narrowly missed to add independent prognostic information (P = 0.0815) for prostate-specific antigen recurrence. CONCLUSION: High intratumoral mast cell density is associated with favorable tumor characteristics and good prognosis in prostate cancer. This finding is consistent with a role of mast cells in the immunological host-defense reaction on prostate cancer. Triggering mast cell activity might expand immunotherapeutic strategies in prostate cancer.

Carbon pools and poverty peaks in Lao PDR

Reducing Emissions from Deforestation and forest Degradation and enhancing forest carbon stocks in developing countries (REDD+) is heavily promoted in Laos. REDD+ is often perceived as an opportunity to jointly address climate change and poverty and, therefore, could come timely for Laos to combine its prominent national target of poverty eradication with global climate mitigation efforts. Countrywide planning of the right approaches to REDD+ combined with poverty alleviation requires knowledge of the spatial combination of poverty and carbon stocks at the national level. This study combined spatial information on carbon stored in vegetation and on poverty and created carbon-poverty typologies for the whole country at the village level. We found that 11% of the villages of Laos have high to very high average village-level carbon stock densities and a predominantly poor population. These villages cover 20% of the territory and are characterized by low population density. Shifting cultivation areas in the northwestern parts of the country have a higher carbon mitigation potential than areas in the central and eastern highlands due to a more favorable climate. Finally, we found that in Laos the majority (58%) of poor people live in areas with low carbon stock densities without major potential to store carbon. Accordingly, REDD+ cannot be considered a core instrument for poverty alleviation. The carbon-poverty typologies presented here provide answers to basic questions related to planning and managing of REDD+. They could serve as a starting point for the design of systems to monitor both socioeconomic and environmental development at the national level.

Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus

The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices. We found that specific activity patterns in the postsynaptic TC cell induced inhibitory long-term potentiation (iLTP). This iLTP was non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsynaptic burst activity alone. iLTP required postsynaptic dendritic Ca2+ influx evoked by low-threshold Ca2+ spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (−50 mV), which suppressed these low-threshold Ca2+ spikes, induced no plasticity. The postsynaptic dendritic Ca2+ increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylyl cyclase, resulting in the presynaptic expression of iLTP. The dependence of iLTP on the membrane potential and therefore on the postsynaptic discharge mode suggests that this form of iLTP might occur during sleep, when TC cells discharge in bursts. Therefore, iLTP might be involved in sleep state-dependent modulation of thalamic information processing and thalamic oscillations.

Internet-based individually versus group guided self-help treatment for social anxiety disorder: protocol of a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common mental disorders and causes subjective suffering and economic burden worldwide. Although effective treatments are available, a lot of cases go untreated. Internet-based self-help is a low-threshold and flexible treatment alternative for SAD. Various studies have already shown that internet-based self-help can be effective to reduce social phobic symptoms significantly. Most of the interventions tested include therapist support, whereas the role of peer support within internet-based self-help has not yet been fully understood. There is evidence suggesting that patients' mutual exchange via integrated discussion forums can increase the efficacy of internet-based treatments. This study aims at investigating the added value of therapist-guided group support on the treatment outcome of internet-based self-help for SAD. METHODS/DESIGN: The study is conducted as a randomized controlled trial. A total of 150 adults with a diagnosis of SAD are randomly assigned to either a waiting-list control group or one of the active conditions. The participants in the two active conditions use the same internet-based self-help program, either with individual support by a psychologist or therapist-guided group support. In the group guided condition, participants can communicate with each other via an integrated, protected discussion forum. Subjects are recruited via topic related websites and links; diagnostic status will be assessed with a telephone interview. The primary outcome variables are symptoms of SAD and diagnostic status after the intervention. Secondary endpoints are general symptomology, depression, quality of life, as well as the primary outcome variables 6 months later. Furthermore, process variables such as group processes, the change in symptoms and working alliance will be studied. DISCUSSION: The results of this study should indicate whether group-guided support could enhance the efficacy of an internet-based self-help treatment for SAD. This novel treatment format, if shown effective, could represent a cost-effective option and could further be modified to treat other conditions, as well.

Optimal dose levels in screening chest CT for unimpaired detection and volumetry of lung nodules, with and without computer assisted detection at minimal patient radiation

OBJECTIVES The aim of this phantom study was to minimize the radiation dose by finding the best combination of low tube current and low voltage that would result in accurate volume measurements when compared to standard CT imaging without significantly decreasing the sensitivity of detecting lung nodules both with and without the assistance of CAD. METHODS An anthropomorphic chest phantom containing artificial solid and ground glass nodules (GGNs, 5-12 mm) was examined with a 64-row multi-detector CT scanner with three tube currents of 100, 50 and 25 mAs in combination with three tube voltages of 120, 100 and 80 kVp. This resulted in eight different protocols that were then compared to standard CT sensitivity (100 mAs/120 kVp). For each protocol, at least 127 different nodules were scanned in 21-25 phantoms. The nodules were analyzed in two separate sessions by three independent, blinded radiologists and computer-aided detection (CAD) software. RESULTS The mean sensitivity of the radiologists for identifying solid lung nodules on a standard CT was 89.7% ± 4.9%. The sensitivity was not significantly impaired when the tube and current voltage were lowered at the same time, except at the lowest exposure level of 25 mAs/80 kVp [80.6% ± 4.3% (p = 0.031)]. Compared to the standard CT, the sensitivity for detecting GGNs was significantly lower at all dose levels when the voltage was 80 kVp; this result was independent of the tube current. The CAD significantly increased the radiologists' sensitivity for detecting solid nodules at all dose levels (5-11%). No significant volume measurement errors (VMEs) were documented for the radiologists or the CAD software at any dose level. CONCLUSIONS Our results suggest a CT protocol with 25 mAs and 100 kVp is optimal for detecting solid and ground glass nodules in lung cancer screening. The use of CAD software is highly recommended at all dose levels.

Water–montmorillonite systems: Neutron scattering and tracer throughdiffusion studies

Designs for deep geological respositories of nuclear waste include bentonite as a hydraulic and chemisorption buffer material to protect the biosphere from leakage of radionuclides. Bentonite is chosen because it is a cheap, naturally occurring material with the required properties. It consists essentially of montmorillonite, a swelling clay mineral. Upon contact with groundwater such clays can seal the repository by incorporating water in the interlayers of their crystalline structure. The intercalated water exhibits significantly different properties to bulk water in the surrounding interparticle pores, such as lower diffusion coefficients (González Sánchez et. al. 2008). This doctoral thesis presents water distribution and diffusion behavior on various time and space scales in montmorillonite. Experimental results are presented for Na- and Cs-montmorillonite samples with a range of bulk dry densities (0.8 to 1.7 g/cm3). The experimental methods employed were neutron scattering (backscattering, diffraction, time-of-flight), adsorption measurements (water, nitrogen) and tracer-through diffusion. For the tracer experiments the samples were fully saturated via the liquid phase under volume-constrained conditions. In contrast, for the neutron scattering experiments, the samples were hydrated via the vapor phase and subsequently compacted, leaving a significant fraction of interparticle pores unfilled with water. Owing to these differences in saturation, the water contents of the samples for neutron scattering were characterized by gravimetry whereas those for the tracer experiments were obtained from the bulk dry density. The amount of surface water in interlayer pores could be successfully discriminated from the amount of bulk-like water in interparticle pores in Na- and Csmontmorillonite using neutron spectroscopy. For the first time in the literature, the distribution of water between these two pore environments was deciphered as a function of gravimetric water content. The amount was compared to a geometrical estimation of the amount of interlayer and interparticle water determined by neutron diffraction and adsorption measurements. The relative abundances of the 1 to 4 molecular water layers in the interlayer were determined from the area ratios of the (001)-diffraction peaks. Depending on the characterization method, different fractions of surface water and interlayer water were obtained. Only surface and interlayer water exists in amontmorillonite with water contents up to 0.18 g/g according to spectroscopic measurements and up to 0.32 g/g according to geometrical estimations, respectively. At higher water contents, bulk-like and interparticle water also exists. The amounts increase monotonically, but not linearly, from zero to 0.33 g/g for bulk-like water and to 0.43 g/g for interparticle water. It was found that water most likely redistributes between the surface and interlayer sites during the spectroscopic measurements and therefore the reported fraction is relevant only below about -10 ºC (Anderson, 1967). The redistribution effect can explain the discrepancy in fractions between the methods. In a novel approach the fractions of water in different pore environments were treated as a fixed parameter to derive local diffusion coefficients for water from quasielastic neutron scattering data, in particular for samples with high water contents. Local diffusion coefficients were obtained for the 1 to 4 molecular water layers in the interlayer of 0.5·10–9, 0.9·10–9, 1.5·10–9 and 1.4·10–9 m²/s, respectively, taking account of the different water fractions (molecular water layer, bulk-like water). The diffusive transport of 22Na and HTO through Na-montmorillonite was measured on the laboratory experimental scale (i.e. cm, days) by tracer through-diffusion experiments. We confirmed that diffusion of HTO is independent of the ionic strength of the external solution in contact with the clay sample but dependent on the bulk dry density. In contrast, the diffusion of 22Na was found to depend on both the ionic strength of the pore solution and on the bulk dry density. The ratio of the pore and surface diffusion could be experimentally determined for 22Na from the dependence of the diffusion coefficient on the ionic strength. Activation energies were derived from the temperaturedependent diffusion coefficients via the Arrhenius relation. In samples with high bulk dry density the activation energies are slightly higher than those of bulk water whereas in low density samples they are lower. The activation energies as a function of ionic strengths of the pore solutions are similar for 22Na and HTO. The facts that (i) the slope of the logarithmic effective diffusion coefficients as a function of the logarithmic ionic strength is less than unity for low bulk dry densities and (ii) two water populations can be observed for high gravimetric water contents (low bulk dry densities) support the interlayer and interparticle porosity model proposed by Glaus et al. (2007), Bourg et al. (2006, 2007) and Gimmi and Kosakowski (2011).

Internet-based stress management for women with preterm labour: a case-based experience report

Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women.

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis.

Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase: effect of a low-tube-voltage, high-tube-current CT technique--preliminary results

To intraindividually compare a low-tube-voltage (80 kVp), high-tube-current (675 mA) computed tomographic (CT) technique with a high-tube-voltage (140 kVp) CT protocol for the detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase.

Low-tube-voltage, high-tube-current multidetector abdominal CT: improved image quality and decreased radiation dose with adaptive statistical iterative reconstruction algorithm--initial clinical experience

To investigate whether an adaptive statistical iterative reconstruction (ASIR) algorithm improves the image quality at low-tube-voltage (80-kVp), high-tube-current (675-mA) multidetector abdominal computed tomography (CT) during the late hepatic arterial phase.